DOI: 10.1002/ijc.2910060207. Inhibitory effects of anti‐tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells <i>in vitro</i>

Inhibitory effects of anti‐tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells in vitro

10.1002/ijc.2910060207

Crossref journal-article

Wiley

International Journal of Cancer (311)

Abstract

AbstractThe inhibitory effects of anti‐tumor, bacterial filament forming platinum compounds, Cis‐Pt(II) (NH3)2Cl2 (A), Cis‐Pt(IV) (NH3)2Cl4 (B), and Pt(II) (NH2)2(CH2)2Cl2(C) on DNA, RNA and protein syntheses was measured by the incorporation of 3H‐thymidine, 3H‐uridine, and 3H‐L‐leucine, respectively, into an acid‐insoluble polymer in human amnion AV3 cells. Compound A, the most effective tumor‐inhibiting platinum compound, was shown to selectively inhibit DNA synthesis below 5μM and to inhibit 3H‐thymidine incorporation more rapidly than 3H‐uridine or 3H‐leucine incorporation at 25μM. Like A, compounds B and C were also shown to inhibit all three processes after a 24‐hour period of treatment at 25μM. A correlation was established between the relative anti‐tumor effectiveness of compounds A, B, and C and the extent of their inhibitory effects. On the other hand, two non‐tumor‐inhibiting platinum compounds, [Pt(II) (NH3)4]Cl2 (D) and Trans‐Pt(IV) (NH3)2Cl4 (E) had no inhibitory effects, except compound E, which exhibited a rapid initial inhibition of 3H‐L‐leucine incorporation at 100μM. The inhibition of 3H‐thymidine incorporation into cells pretreated 4 h with 5μM of compounds A, B, and C was shown to be irreversible. Finally the inhibition of the incorporation of 3H‐thymidine into DNA by A was shown not to be caused by the inhibition of the uptake of the tracer into the acid‐soluble pool. A number of possible explanations for the greater sensitivity of DNA synthesis and the sequential inhibition of DNA, RNA and protein synthesis at higher concentrations are suggested.

Bibliography

Harder, H. C., & Rosenberg, B. (1970). Inhibitory effects of antiâtumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells in vitro. International Journal of Cancer, 6(2), 207â216. Portico.

Authors 2

Harold C. Harder (first)
Barnett Rosenberg (additional)

References 20 Referenced 310

10.2307/3571896
10.1016/S0021-9258(18)55583-6
Harder H. C.andRosenberg B Inhibition of DNA polymerase in vitro and DNA synthesis in vivo in human amnionic AV3cells treated with tumor inhibiting platinum compounds.Third International Biophysics Congress of the International Union for Pure and Applied Biophysics Cambridge Mass. USA. Aug. 29‐Sept. 3 1969 p.31.
Howle J. A.andGale G. R. Cis dichlorodiammine platinum II: persistent and selective inhibition of deoxyribonucleic acid synthesis in vivo. Submitted for publication.
10.1002/9780470132388.ch63
{'key': 'e_1_2_1_7_1', 'first-page': '1301', 'article-title': 'Action of hydroxyurea on the nucleic acid metabolism and the viability of HeLa cells', 'volume': '27', 'author': 'Kim J. H.', 'year': '1967', 'journal-title': 'Cancer Res.'} / Cancer Res. / Action of hydroxyurea on the nucleic acid metabolism and the viability of HeLa cells by Kim J. H. (1967)
Kociba R. J. Sleight S. D.andRosenberg B Inhibition of Dunning ascitic leukemia and Walker 256 carcinosarcoma with cis‐platinum (II) diammino dichloride.Cancer Chem. Rep. In Press (1970).
{'key': 'e_1_2_1_9_1', 'first-page': '95', 'article-title': 'Invest. Sektova Platini i Drug. Glagorod. Metal., Inst. Obshchei i Neorg. Kleim', 'volume': '20', 'author': 'Lebedinskii V. V.', 'year': '1947', 'journal-title': 'Akad. Nauk. USSR'} / Akad. Nauk. USSR / Invest. Sektova Platini i Drug. Glagorod. Metal., Inst. Obshchei i Neorg. Kleim by Lebedinskii V. V. (1947)
{'key': 'e_1_2_1_10_1', 'first-page': '124', 'article-title': 'Inhibition of DNA synthesis by hydroxyurea', 'volume': '27', 'author': 'Pfeiffer S. E.', 'year': '1967', 'journal-title': 'Cancer Res.'} / Cancer Res. / Inhibition of DNA synthesis by hydroxyurea by Pfeiffer S. E. (1967)
10.1083/jcb.28.1.139
{'key': 'e_1_2_1_12_1', 'first-page': '716', 'article-title': 'Platinum induced filamentous growth in', 'volume': '93', 'author': 'Rosenberg B.', 'year': '1967', 'journal-title': 'Escherichia coli. J. Bact.'} / Escherichia coli. J. Bact. / Platinum induced filamentous growth in by Rosenberg B. (1967)
Rosenberg B.andVanCamp L The successful regression of large solid sarcoma 180 tumors by platinum compounds.Cancer Res. In Press (1970).
10.1016/S0021-9258(18)96186-7 / J. biol. Chem. / The inhibition of growth and cell division in Escherichia coli by different ionic species of platinum (IV) complexes by Rosenberg B. (1967)
10.1038/222385a0
10.1016/0005-2787(66)90099-2
10.1126/science.142.3598.1464
10.1073/pnas.57.5.1275
{'key': 'e_1_2_1_19_1', 'first-page': '1082', 'article-title': 'Further studies on the mechanism of action of hydroxyurea', 'volume': '28', 'author': 'Yarbro J. W.', 'year': '1968', 'journal-title': 'Cancer Res.'} / Cancer Res. / Further studies on the mechanism of action of hydroxyurea by Yarbro J. W. (1968)
10.1126/science.146.3648.1172
{'key': 'e_1_2_1_21_1', 'first-page': '526', 'article-title': 'Hydroxyurea induced inhibition of DNA synthesis. Studies in intact cells', 'volume': '27', 'author': 'Young C. W.', 'year': '1967', 'journal-title': 'Cancer Res.'} / Cancer Res. / Hydroxyurea induced inhibition of DNA synthesis. Studies in intact cells by Young C. W. (1967)

Dates

Type	When
Created	18 years, 6 months ago (Feb. 19, 2007, 8:15 a.m.)
Deposited	1 year, 9 months ago (Nov. 12, 2023, 4:39 a.m.)
Indexed	2 months, 3 weeks ago (June 11, 2025, 4:46 a.m.)
Issued	54 years, 11 months ago (Sept. 15, 1970)
Published	54 years, 11 months ago (Sept. 15, 1970)
Published Online	19 years, 1 month ago (July 18, 2006)
Published Print	54 years, 11 months ago (Sept. 15, 1970)

Funders 0

None

BibTeX

@article{Harder_1970, title={Inhibitory effects of anti‐tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells in vitro}, volume={6}, ISSN={1097-0215}, url={http://dx.doi.org/10.1002/ijc.2910060207}, DOI={10.1002/ijc.2910060207}, number={2}, journal={International Journal of Cancer}, publisher={Wiley}, author={Harder, Harold C. and Rosenberg, Barnett}, year={1970}, month=sep, pages={207–216} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        6,
        11
      ]
    ],
    "date-time": "2025-06-11T08:46:14Z",
    "timestamp": 1749631574491
  },
  "reference-count": 20,
  "publisher": "Wiley",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2006,
            7,
            18
          ]
        ],
        "date-time": "2006-07-18T00:00:00Z",
        "timestamp": 1153180800000
      },
      "content-version": "vor",
      "delay-in-days": 13090,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1970,
        9,
        15
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>The inhibitory effects of anti\u2010tumor, bacterial filament forming platinum compounds, Cis\u2010Pt(II) (NH<jats:sub>3</jats:sub>)<jats:sub>2</jats:sub>Cl<jats:sub>2</jats:sub> (A), Cis\u2010Pt(IV) (NH<jats:sub>3</jats:sub>)<jats:sub>2</jats:sub>Cl<jats:sub>4</jats:sub> (B), and Pt(II) (NH<jats:sub>2</jats:sub>)<jats:sub>2</jats:sub>(CH<jats:sub>2</jats:sub>)<jats:sub>2</jats:sub>Cl<jats:sub>2</jats:sub>(C) on DNA, RNA and protein syntheses was measured by the incorporation of <jats:sup>3</jats:sup>H\u2010thymidine, <jats:sup>3</jats:sup>H\u2010uridine, and <jats:sup>3</jats:sup>H\u2010L\u2010leucine, respectively, into an acid\u2010insoluble polymer in human amnion AV<jats:sub>3</jats:sub> cells. Compound A, the most effective tumor\u2010inhibiting platinum compound, was shown to selectively inhibit DNA synthesis below 5\u03bcM and to inhibit <jats:sup>3</jats:sup>H\u2010thymidine incorporation more rapidly than <jats:sup>3</jats:sup>H\u2010uridine or <jats:sup>3</jats:sup>H\u2010leucine incorporation at 25\u03bcM. Like A, compounds B and C were also shown to inhibit all three processes after a 24\u2010hour period of treatment at 25\u03bcM. A correlation was established between the relative anti\u2010tumor effectiveness of compounds A, B, and C and the extent of their inhibitory effects. On the other hand, two non\u2010tumor\u2010inhibiting platinum compounds, [Pt(II) (NH<jats:sub>3</jats:sub>)<jats:sub>4</jats:sub>]Cl<jats:sub>2</jats:sub> (D) and Trans\u2010Pt(IV) (NH<jats:sub>3</jats:sub>)<jats:sub>2</jats:sub>Cl<jats:sub>4</jats:sub> (E) had no inhibitory effects, except compound E, which exhibited a rapid initial inhibition of <jats:sup>3</jats:sup>H\u2010L\u2010leucine incorporation at 100\u03bcM. The inhibition of <jats:sup>3</jats:sup>H\u2010thymidine incorporation into cells pretreated 4 h with 5\u03bcM of compounds A, B, and C was shown to be irreversible. Finally the inhibition of the incorporation of <jats:sup>3</jats:sup>H\u2010thymidine into DNA by A was shown not to be caused by the inhibition of the uptake of the tracer into the acid\u2010soluble pool. A number of possible explanations for the greater sensitivity of DNA synthesis and the sequential inhibition of DNA, RNA and protein synthesis at higher concentrations are suggested.</jats:p>",
  "DOI": "10.1002/ijc.2910060207",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2007,
        2,
        19
      ]
    ],
    "date-time": "2007-02-19T13:15:33Z",
    "timestamp": 1171890933000
  },
  "page": "207-216",
  "source": "Crossref",
  "is-referenced-by-count": 310,
  "title": "Inhibitory effects of anti\u2010tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells <i>in vitro</i>",
  "prefix": "10.1002",
  "volume": "6",
  "author": [
    {
      "given": "Harold C.",
      "family": "Harder",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Barnett",
      "family": "Rosenberg",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2006,
        7,
        18
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.2307/3571896"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)55583-6"
    },
    {
      "key": "e_1_2_1_4_1",
      "unstructured": "Harder H. C.andRosenberg B Inhibition of DNA polymerase in vitro and DNA synthesis in vivo in human amnionic AV3cells treated with tumor inhibiting platinum compounds.Third International Biophysics Congress of the International Union for Pure and Applied Biophysics Cambridge Mass. USA. Aug. 29\u2010Sept. 3 1969 p.31."
    },
    {
      "key": "e_1_2_1_5_1",
      "unstructured": "Howle J. A.andGale G. R. Cis dichlorodiammine platinum II: persistent and selective inhibition of deoxyribonucleic acid synthesis in vivo. Submitted for publication."
    },
    {
      "key": "e_1_2_1_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/9780470132388.ch63"
    },
    {
      "key": "e_1_2_1_7_1",
      "first-page": "1301",
      "article-title": "Action of hydroxyurea on the nucleic acid metabolism and the viability of HeLa cells",
      "volume": "27",
      "author": "Kim J. H.",
      "year": "1967",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_8_1",
      "unstructured": "Kociba R. J. Sleight S. D.andRosenberg B Inhibition of Dunning ascitic leukemia and Walker 256 carcinosarcoma with cis\u2010platinum (II) diammino dichloride.Cancer Chem. Rep. In Press (1970)."
    },
    {
      "key": "e_1_2_1_9_1",
      "first-page": "95",
      "article-title": "Invest. Sektova Platini i Drug. Glagorod. Metal., Inst. Obshchei i Neorg. Kleim",
      "volume": "20",
      "author": "Lebedinskii V. V.",
      "year": "1947",
      "journal-title": "Akad. Nauk. USSR"
    },
    {
      "key": "e_1_2_1_10_1",
      "first-page": "124",
      "article-title": "Inhibition of DNA synthesis by hydroxyurea",
      "volume": "27",
      "author": "Pfeiffer S. E.",
      "year": "1967",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.28.1.139"
    },
    {
      "key": "e_1_2_1_12_1",
      "first-page": "716",
      "article-title": "Platinum induced filamentous growth in",
      "volume": "93",
      "author": "Rosenberg B.",
      "year": "1967",
      "journal-title": "Escherichia coli. J. Bact."
    },
    {
      "key": "e_1_2_1_13_1",
      "unstructured": "Rosenberg B.andVanCamp L The successful regression of large solid sarcoma 180 tumors by platinum compounds.Cancer Res. In Press (1970)."
    },
    {
      "key": "e_1_2_1_14_1",
      "doi-asserted-by": "crossref",
      "first-page": "1347",
      "DOI": "10.1016/S0021-9258(18)96186-7",
      "article-title": "The inhibition of growth and cell division in Escherichia coli by different ionic species of platinum (IV) complexes",
      "volume": "242",
      "author": "Rosenberg B.",
      "year": "1967",
      "journal-title": "J. biol. Chem."
    },
    {
      "key": "e_1_2_1_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/222385a0"
    },
    {
      "key": "e_1_2_1_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0005-2787(66)90099-2"
    },
    {
      "key": "e_1_2_1_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.142.3598.1464"
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.57.5.1275"
    },
    {
      "key": "e_1_2_1_19_1",
      "first-page": "1082",
      "article-title": "Further studies on the mechanism of action of hydroxyurea",
      "volume": "28",
      "author": "Yarbro J. W.",
      "year": "1968",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.146.3648.1172"
    },
    {
      "key": "e_1_2_1_21_1",
      "first-page": "526",
      "article-title": "Hydroxyurea induced inhibition of DNA synthesis. Studies in intact cells",
      "volume": "27",
      "author": "Young C. W.",
      "year": "1967",
      "journal-title": "Cancer Res."
    }
  ],
  "container-title": "International Journal of Cancer",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.2910060207",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.2910060207",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        11,
        12
      ]
    ],
    "date-time": "2023-11-12T09:39:53Z",
    "timestamp": 1699781993000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/ijc.2910060207"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1970,
        9,
        15
      ]
    ]
  },
  "references-count": 20,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          1970,
          9,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/ijc.2910060207"
  ],
  "URL": "http://dx.doi.org/10.1002/ijc.2910060207",
  "relation": {},
  "ISSN": [
    "0020-7136",
    "1097-0215"
  ],
  "subject": [],
  "container-title-short": "Intl Journal of Cancer",
  "published": {
    "date-parts": [
      [
        1970,
        9,
        15
      ]
    ]
  }
}